Human trophoblast invasion. Autocrine control and paracrine modulation

Development of the human placenta involves rapid invasion of the uterine wall by fetal trophoblasts, a process with certain similarities to tumor cell invasion. Unlike tumor invasion, however, this unique interaction between genetically dissimilar trophoblast and uterine cells is closely regulated and limited both temporally and spatially by mechanisms that are largely unknown. We have used a combination of two experimental approaches to study this process: immunolocalization using tissue sections to investigate trophoblast invasion in vivo, and a cell culture model that allows manipulation of the invasion process in vitro. The results show that invading trophoblasts express activated forms of metalloproteinases, adhesion molecules and the novel class I histocompatibility antigen, HLA-G, in a highly regulated manner during invasion. The behavior of cytotrophoblasts in vitro, removed from the influences of uterine cells, closely parallels their behavior in vivo, suggesting the existence of autocrine control mechanisms. However, studies examining the effect of growth factors and cytokines on trophoblast invasion suggest that molecules of uterine origin can modify this process. Thus, we hypothesize that the intrinsic invasiveness of these cells is controlled, at least in part, by the specialized environment of the uterus. Future studies will concentrate on identifying these factors and the specific trophoblast functions they modify.